R libraries.

library(ggplot2)
library(ggrepel)
library(ggpubr)
library(stringr)
library(RColorBrewer)
library(goseq)
library(fgsea)

library(dplyr)
library(data.table)
theme_set(theme_classic())

Read in DE results

res = fread("results/2023_12_DEseq2.tsv.gz", data.table = FALSE)
dim(res)
## [1] 25835   145
res[1:2,1:5]
##           gene_ID PrS_nor_POU2F3_CE_baseMean PrS_nor_POU2F3_CE_log2FoldChange
## 1 ENSG00000000003                       1150                          -0.0175
## 2 ENSG00000000419                       1210                          -0.3820
##   PrS_nor_POU2F3_CE_lfcSE PrS_nor_POU2F3_CE_stat
## 1                  0.0683                 -0.256
## 2                  0.1210                 -3.160
items = names(res)[grep("_padj", names(res))]
items
##  [1] "PrS_nor_POU2F3_CE_padj"  "PrS_nor_POU2F3_KO_padj" 
##  [3] "PrS_nor_POU2F3_PTC_padj" "PrS_nor_PPARG_CE_padj"  
##  [5] "PrS_nor_PPARG_KO_padj"   "PrS_nor_PPARG_PTC_padj" 
##  [7] "PrS_nor_GCM1_CE_padj"    "PrS_nor_GCM1_KO_padj"   
##  [9] "PrS_nor_GCM1_PTC_padj"   "PrS_nor_FOSB_CE_padj"   
## [11] "PrS_nor_FOSB_KO_padj"    "PrS_nor_FOSB_PTC_padj"  
## [13] "PrS_nor_EPAS1_CE_padj"   "PrS_nor_EPAS1_KO_padj"  
## [15] "PrS_nor_EPAS1_PTC_padj"  "PrS_nor_GRHL1_CE_padj"  
## [17] "PrS_nor_GRHL1_KO_padj"   "PrS_nor_GRHL1_PTC_padj" 
## [19] "PrS_hyp_EPAS1_CE_padj"   "PrS_hyp_EPAS1_KO_padj"  
## [21] "PrS_hyp_EPAS1_PTC_padj"  "ExM_nor_ISL1_CE_padj"   
## [23] "ExM_nor_ISL1_KO_padj"    "ExM_nor_ISL1_PTC_padj"
gene_sets = list()
for(it1 in items){
  id1 = gsub("_padj", "", it1)
  
  res_k = res[,c(1, grep(id1, names(res)))]
  names(res_k) = gsub(paste0(id1, "_"), "", names(res_k))
  
  w_up = which(res_k$log2FoldChange > log2(1.5) & res_k$padj < 0.01)
  w_down = which(res_k$log2FoldChange < -log2(1.5) & res_k$padj < 0.01)
  
  gene_sets[[paste0(id1, "_up")]] = res_k$gene_ID[w_up]
  gene_sets[[paste0(id1, "_down")]] = res_k$gene_ID[w_down]
}

sapply(gene_sets, length)
##    PrS_nor_POU2F3_CE_up  PrS_nor_POU2F3_CE_down    PrS_nor_POU2F3_KO_up 
##                     299                     113                      17 
##  PrS_nor_POU2F3_KO_down   PrS_nor_POU2F3_PTC_up PrS_nor_POU2F3_PTC_down 
##                       6                       1                       1 
##     PrS_nor_PPARG_CE_up   PrS_nor_PPARG_CE_down     PrS_nor_PPARG_KO_up 
##                    1672                    1976                     981 
##   PrS_nor_PPARG_KO_down    PrS_nor_PPARG_PTC_up  PrS_nor_PPARG_PTC_down 
##                    1319                    1314                    1980 
##      PrS_nor_GCM1_CE_up    PrS_nor_GCM1_CE_down      PrS_nor_GCM1_KO_up 
##                    1907                    2639                    1494 
##    PrS_nor_GCM1_KO_down     PrS_nor_GCM1_PTC_up   PrS_nor_GCM1_PTC_down 
##                    2276                    1339                    2233 
##      PrS_nor_FOSB_CE_up    PrS_nor_FOSB_CE_down      PrS_nor_FOSB_KO_up 
##                      37                      13                     167 
##    PrS_nor_FOSB_KO_down     PrS_nor_FOSB_PTC_up   PrS_nor_FOSB_PTC_down 
##                      12                     344                     150 
##     PrS_nor_EPAS1_CE_up   PrS_nor_EPAS1_CE_down     PrS_nor_EPAS1_KO_up 
##                     480                     353                       8 
##   PrS_nor_EPAS1_KO_down    PrS_nor_EPAS1_PTC_up  PrS_nor_EPAS1_PTC_down 
##                      11                      56                      69 
##     PrS_nor_GRHL1_CE_up   PrS_nor_GRHL1_CE_down     PrS_nor_GRHL1_KO_up 
##                     776                    1480                     642 
##   PrS_nor_GRHL1_KO_down    PrS_nor_GRHL1_PTC_up  PrS_nor_GRHL1_PTC_down 
##                     986                    1769                    2251 
##     PrS_hyp_EPAS1_CE_up   PrS_hyp_EPAS1_CE_down     PrS_hyp_EPAS1_KO_up 
##                    1625                    1191                     957 
##   PrS_hyp_EPAS1_KO_down    PrS_hyp_EPAS1_PTC_up  PrS_hyp_EPAS1_PTC_down 
##                     541                    1070                     608 
##      ExM_nor_ISL1_CE_up    ExM_nor_ISL1_CE_down      ExM_nor_ISL1_KO_up 
##                    1023                     466                     918 
##    ExM_nor_ISL1_KO_down     ExM_nor_ISL1_PTC_up   ExM_nor_ISL1_PTC_down 
##                     487                     696                     349

Read in gene annotation

gene_info = fread("data/gencode_v44_basic_gene_info.tsv", data.table = FALSE)
dim(gene_info)
## [1] 62700     8
gene_info[1:2,]
##               geneId  chr strand     start       end ensembl_gene_id
## 1 ENSG00000000003.16 chrX      - 100627108 100637104 ENSG00000000003
## 2  ENSG00000000005.6 chrX      + 100584936 100599885 ENSG00000000005
##   hgnc_symbol                                       description
## 1      TSPAN6 tetraspanin 6 [Source:HGNC Symbol;Acc:HGNC:11858]
## 2        TNMD   tenomodulin [Source:HGNC Symbol;Acc:HGNC:17757]
table(res$gene_ID %in% gene_info$ensembl_gene_id)
## 
## FALSE  TRUE 
##     7 25828
gene_info = gene_info[gene_info$ensembl_gene_id %in% res$gene_ID,]
dim(gene_info)
## [1] 25828     8
gene_info[1:2,]
##               geneId   chr strand     start       end ensembl_gene_id
## 1 ENSG00000000003.16  chrX      - 100627108 100637104 ENSG00000000003
## 3 ENSG00000000419.14 chr20      -  50934867  50959140 ENSG00000000419
##   hgnc_symbol
## 1      TSPAN6
## 3        DPM1
##                                                                                      description
## 1                                              tetraspanin 6 [Source:HGNC Symbol;Acc:HGNC:11858]
## 3 dolichyl-phosphate mannosyltransferase subunit 1, catalytic [Source:HGNC Symbol;Acc:HGNC:3005]
t_symbol = table(gene_info$hgnc_symbol)
table(t_symbol)
## t_symbol
##     1     2  5749 
## 20012     1     1
t_symbol[t_symbol > 1]
## 
##         GOLGA8M 
##    5749       2
gene_info = gene_info[gene_info$hgnc_symbol %in% names(t_symbol)[t_symbol==1],]
dim(gene_info)
## [1] 20012     8

Prepare gene set information

Gene set annotations (by gene symbols) were downloaded from MSigDB website.

gmtfile = list()
gmtfile[["reactome"]] = "gene_annotation/c2.cp.reactome.v2023.2.Hs.symbols.gmt"
gmtfile[["go_bp"]]    = "gene_annotation/c5.go.bp.v2023.2.Hs.symbols.gmt"

pathways = list()
for(k1 in names(gmtfile)){
  pathways[[k1]] = gmtPathways(gmtfile[[k1]])
}

names(pathways)
## [1] "reactome" "go_bp"
sapply(pathways, length)
## reactome    go_bp 
##     1692     7647

Filter gene sets for size between 10 and 500.

lapply(pathways, function(v){
  quantile(sapply(v, length), probs = seq(0, 1, 0.1), na.rm = TRUE)
})
## $reactome
##     0%    10%    20%    30%    40%    50%    60%    70%    80%    90%   100% 
##    5.0    7.0    9.0   12.0   17.0   23.0   31.0   44.0   71.8  120.9 1463.0 
## 
## $go_bp
##     0%    10%    20%    30%    40%    50%    60%    70%    80%    90%   100% 
##    5.0    6.0    8.0   10.0   14.0   19.0   29.0   46.0   80.8  183.0 1966.0
for(k1 in names(pathways)){
  p1 = pathways[[k1]]
  pathways[[k1]] = p1[sapply(p1, length) %in% 10:500]
}

Conduct enrichment analysis

dim(gene_info)
## [1] 20012     8
max_n2kp = 10
goseq_res = NULL

for(k in 1:length(gene_sets)){
  if(length(gene_sets[[k]]) < 10) { next }
  
  print(k)
  set_k = names(gene_sets)[k]

  genes = gene_info$ensembl_gene_id %in% gene_sets[[k]]
  names(genes) = gene_info$hgnc_symbol
  table(genes)
  
  pwf = nullp(genes, "hg38", "geneSymbol")

  for(k1 in names(pathways)){
    p1 = pathways[[k1]]
    res1 = goseq(pwf, "hg38", "geneSymbol", 
                 gene2cat=goseq:::reversemapping(p1))
    res1$FDR  = p.adjust(res1$over_represented_pvalue, method="BH")
    
    nD = sum(res1$FDR < 0.05)
    
    if(nD > 0){
      res1 = res1[order(res1$FDR),][1:min(nD, max_n2kp),]
      res1$category = gsub("REACTOME_|GOBP_", "", res1$category)
      res1$category = gsub("_", " ", res1$category)
      res1$category = tolower(res1$category)
      res1$category = substr(res1$category, start=1, stop=120)
      goseq_res[[set_k]][[k1]] = res1
    }
  }
}
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Conduct enrichment analysis

for(n1 in names(goseq_res)){
  print(n1)
  print(goseq_res[[n1]])
}
## [1] "PrS_nor_POU2F3_CE_up"
## $reactome
##                                              category over_represented_pvalue
## 743 o glycosylation of tsr domain containing proteins            1.591739e-05
##     under_represented_pvalue numDEInCat numInCat        FDR
## 743                0.9999987          7       38 0.02110646
## 
## $go_bp
##                               category over_represented_pvalue
## 82       ameboidal type cell migration            2.719625e-11
## 5112                  tissue migration            3.096940e-10
## 917         endothelial cell migration            8.572129e-09
## 1687            mesenchyme development            1.041989e-08
## 38   actomyosin structure organization            1.949320e-07
## 4970            sprouting angiogenesis            4.153035e-07
## 403         cell cell signaling by wnt            4.839647e-07
## 1877         muscle tissue development            5.932310e-07
## 1680  mesenchymal cell differentiation            8.013422e-07
## 4901  smad protein signal transduction            1.727102e-06
##      under_represented_pvalue numDEInCat numInCat          FDR
## 82                  1.0000000         31      415 1.446025e-07
## 5112                1.0000000         25      300 8.233216e-07
## 917                 1.0000000         19      210 1.385064e-05
## 1687                1.0000000         23      297 1.385064e-05
## 38                  1.0000000         17      200 2.072907e-04
## 4970                0.9999999         13      124 3.676058e-04
## 403                 0.9999999         25      434 3.676058e-04
## 1877                0.9999998         24      400 3.942762e-04
## 1680                0.9999998         18      240 4.734152e-04
## 4901                0.9999998         10       75 9.183003e-04
## 
## [1] "PrS_nor_POU2F3_CE_down"
## $reactome
##               category over_represented_pvalue under_represented_pvalue
## 129 cardiac conduction            3.106446e-05                0.9999977
## 666 muscle contraction            4.888954e-05                0.9999950
##     numDEInCat numInCat        FDR
## 129          6      122 0.03241377
## 666          7      193 0.03241377
## 
## $go_bp
##                                         category over_represented_pvalue
## 3396                   potassium ion homeostasis            8.200227e-06
## 1358 inorganic ion import across plasma membrane            1.443782e-05
## 4923    sodium ion export across plasma membrane            2.116157e-05
## 1333               import across plasma membrane            2.446447e-05
## 1411     intracellular potassium ion homeostasis            2.594676e-05
## 3397 potassium ion import across plasma membrane            3.204801e-05
##      under_represented_pvalue numDEInCat numInCat        FDR
## 3396                0.9999998          4       28 0.02759179
## 1358                0.9999991          6      117 0.02759179
## 4923                0.9999998          3       12 0.02759179
## 1333                0.9999977          7      189 0.02759179
## 1411                0.9999997          3       13 0.02759179
## 3397                0.9999990          4       40 0.02839988
## 
## [1] "PrS_nor_PPARG_CE_up"
## $reactome
##                     category over_represented_pvalue under_represented_pvalue
## 551 intraflagellar transport            1.789545e-05                0.9999965
##     numDEInCat numInCat        FDR
## 551         14       49 0.02372936
## 
## $go_bp
##                                        category over_represented_pvalue
## 18                  actin filament organization            1.506530e-08
## 38            actomyosin structure organization            1.351979e-07
## 3641 regulation of actin filament based process            1.353706e-07
## 1239                        heart morphogenesis            1.782490e-07
## 4911               smoothened signaling pathway            4.385962e-07
## 629                         cilium organization            4.112483e-06
## 371                       cartilage development            4.536120e-06
## 659               connective tissue development            4.610018e-06
## 1687                     mesenchyme development            5.199423e-06
## 1877                  muscle tissue development            6.634200e-06
##      under_represented_pvalue numDEInCat numInCat          FDR
## 18                  1.0000000         73      441 0.0000801022
## 38                  1.0000000         41      200 0.0002369375
## 3641                1.0000000         61      362 0.0002369375
## 1239                1.0000000         49      255 0.0002369375
## 4911                0.9999999         32      143 0.0004664032
## 629                 0.9999981         63      413 0.0030639330
## 371                 0.9999983         36      188 0.0030639330
## 659                 0.9999981         46      263 0.0030639330
## 1687                0.9999978         50      297 0.0030717037
## 1877                0.9999969         62      400 0.0035274040
## 
## [1] "PrS_nor_PPARG_CE_down"
## $reactome
##                                       category over_represented_pvalue
## 947 response of eif2ak1 hri to heme deficiency            1.427068e-05
##     under_represented_pvalue numDEInCat numInCat        FDR
## 947                0.9999988          9       15 0.01892293
## 
## $go_bp
##                                            category over_represented_pvalue
## 2016 negative regulation of cell substrate adhesion            1.259623e-06
## 4056               regulation of lipid localization            4.251012e-06
## 3066 positive regulation of lipid metabolic process            5.731349e-06
## 4891              skeletal muscle organ development            1.109147e-05
## 3482         protein localization to cell periphery            1.226713e-05
## 3065      positive regulation of lipid localization            1.391728e-05
## 456               cellular ketone metabolic process            1.525635e-05
## 3063 positive regulation of lipid catabolic process            1.664113e-05
## 2182            negative regulation of mapk cascade            2.072601e-05
## 2601                        organic anion transport            2.092906e-05
##      under_represented_pvalue numDEInCat numInCat         FDR
## 2016                0.9999997         20       55 0.006697414
## 4056                0.9999984         37      151 0.009854943
## 3066                0.9999980         33      130 0.009854943
## 4891                0.9999955         39      169 0.009854943
## 3482                0.9999939         65      341 0.009854943
## 3065                0.9999955         27      100 0.009854943
## 456                 0.9999934         43      198 0.009854943
## 3063                0.9999978         11       24 0.009854943
## 2182                0.9999917         36      155 0.009854943
## 2601                0.9999889         72      391 0.009854943
## 
## [1] "PrS_nor_PPARG_KO_up"
## $go_bp
##                                                         category
## 5000                          striated muscle tissue development
## 1687                                      mesenchyme development
## 1680                            mesenchymal cell differentiation
## 2955 positive regulation of epithelial to mesenchymal transition
## 361                                 cardiac septum morphogenesis
## 3897          regulation of epithelial to mesenchymal transition
## 954                         epithelial to mesenchymal transition
## 1877                                   muscle tissue development
## 18                                   actin filament organization
## 2610                                                ossification
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 5000            2.945467e-09                        1         38      241
## 1687            9.993698e-09                        1         42      297
## 1680            1.138978e-08                        1         37      240
## 2955            1.831744e-08                        1         16       55
## 361             1.911867e-08                        1         19       71
## 3897            5.610694e-08                        1         21       97
## 954             5.959661e-08                        1         28      161
## 1877            6.947748e-08                        1         49      400
## 18              9.102246e-08                        1         51      441
## 2610            9.577910e-08                        1         48      392
##               FDR
## 5000 1.566105e-05
## 1687 2.018649e-05
## 1680 2.018649e-05
## 2955 2.033079e-05
## 361  2.033079e-05
## 3897 4.526788e-05
## 954  4.526788e-05
## 1877 4.617647e-05
## 18   5.092575e-05
## 2610 5.092575e-05
## 
## [1] "PrS_nor_PPARG_KO_down"
## $go_bp
##                                            category over_represented_pvalue
## 4056               regulation of lipid localization            1.540138e-06
## 450                  cellular component maintenance            5.108457e-06
## 4923       sodium ion export across plasma membrane            5.878393e-06
## 3066 positive regulation of lipid metabolic process            7.478897e-06
## 5297                      vitamin metabolic process            7.577194e-06
## 3065      positive regulation of lipid localization            1.079129e-05
## 5241                             vascular transport            1.389572e-05
## 456               cellular ketone metabolic process            1.508202e-05
## 1180              glycerolipid biosynthetic process            1.822499e-05
## 3063 positive regulation of lipid catabolic process            2.097258e-05
##      under_represented_pvalue numDEInCat numInCat         FDR
## 4056                0.9999995         29      151 0.008057588
## 450                 0.9999989         17       68 0.008057588
## 4923                0.9999997          7       12 0.008057588
## 3066                0.9999977         25      130 0.008057588
## 5297                0.9999980         21       99 0.008057588
## 3065                0.9999970         21      100 0.009562880
## 5241                0.9999964         19       86 0.010023888
## 456                 0.9999943         32      198 0.010023888
## 1180                0.9999926         36      237 0.010766918
## 3063                0.9999977          9       24 0.011151121
## 
## [1] "PrS_nor_PPARG_PTC_up"
## $reactome
##                                                             category
## 147                                           cell cycle checkpoints
## 654                                       mitotic spindle checkpoint
## 944                          resolution of sister chromatid cohesion
## 960                                     rho gtpases activate formins
## 958                                             rho gtpase effectors
## 593                                                          m phase
## 255 deposition of new cenpa containing nucleosomes at the centromere
## 652                                             mitotic prometaphase
## 274                                diseases of programmed cell death
## 191                             condensation of prophase chromosomes
##     over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 147            8.971731e-14                        1         58      288
## 654            1.226406e-11                        1         31      110
## 944            1.344656e-11                        1         33      122
## 960            6.501111e-11                        1         34      136
## 958            2.556359e-10                        1         55      316
## 593            3.047557e-10                        1         65      410
## 255            4.467555e-10                        1         22       71
## 652            2.832784e-09                        1         40      199
## 274            1.617981e-08                        1         25      103
## 191            1.488018e-07                        1         19       72
##              FDR
## 147 1.189652e-10
## 654 5.943380e-09
## 944 5.943380e-09
## 960 2.155118e-08
## 958 6.735102e-08
## 593 6.735102e-08
## 255 8.462825e-08
## 652 4.695339e-07
## 274 2.383825e-06
## 191 1.808518e-05
## 
## $go_bp
##                                       category over_represented_pvalue
## 1789                  mitotic nuclear division            5.122981e-13
## 1793      mitotic sister chromatid segregation            1.344423e-12
## 4209            regulation of nuclear division            1.505956e-12
## 2005 negative regulation of cell cycle process            1.637366e-12
## 409            cell cycle checkpoint signaling            1.664573e-12
## 4885              sister chromatid segregation            2.134660e-12
## 2002         negative regulation of cell cycle            7.969800e-12
## 2196 negative regulation of mitotic cell cycle            1.298933e-11
## 2592                         organelle fission            1.591393e-11
## 3811      regulation of chromosome segregation            1.619315e-11
##      under_represented_pvalue numDEInCat numInCat          FDR
## 1789                        1         56      273 1.770107e-09
## 1793                        1         44      186 1.770107e-09
## 4209                        1         36      136 1.770107e-09
## 2005                        1         57      290 1.770107e-09
## 409                         1         44      190 1.770107e-09
## 4885                        1         49      225 1.891664e-09
## 2002                        1         65      366 6.053632e-09
## 2196                        1         47      223 8.609898e-09
## 2592                        1         75      461 8.609898e-09
## 3811                        1         33      125 8.609898e-09
## 
## [1] "PrS_nor_PPARG_PTC_down"
## $go_bp
##                                            category over_represented_pvalue
## 456               cellular ketone metabolic process            2.671879e-08
## 4056               regulation of lipid localization            3.417867e-08
## 4891              skeletal muscle organ development            1.243865e-07
## 3065      positive regulation of lipid localization            8.967724e-07
## 3066 positive regulation of lipid metabolic process            1.148270e-06
## 3063 positive regulation of lipid catabolic process            1.438808e-06
## 1167                      glucose metabolic process            2.879317e-06
## 2016 negative regulation of cell substrate adhesion            4.047215e-06
## 5241                             vascular transport            4.627484e-06
## 4057          regulation of lipid metabolic process            5.894932e-06
##      under_represented_pvalue numDEInCat numInCat          FDR
## 456                 1.0000000         49      198 0.0000908640
## 4056                1.0000000         41      151 0.0000908640
## 4891                1.0000000         43      169 0.0002204543
## 3065                0.9999997         29      100 0.0011920347
## 3066                0.9999996         34      130 0.0012210703
## 3063                0.9999998         12       24 0.0012750238
## 1167                0.9999989         40      174 0.0021870472
## 2016                0.9999991         19       55 0.0026898805
## 5241                0.9999987         25       86 0.0027338148
## 4057                0.9999973         60      306 0.0030042788
## 
## [1] "PrS_nor_GCM1_CE_up"
## $reactome
##                                                                                           category
## 467                                                                     hdacs deacetylate histones
## 283                                                                                dna methylation
## 1126                                                    sirt1 negatively regulates rrna expression
## 191                                                           condensation of prophase chromosomes
## 13   activated pkn1 stimulates transcription of ar androgen receptor regulated genes klk2 and klk3
## 828                                                               prc2 methylates histones and dna
## 607                                                                          meiotic recombination
## 87                                        assembly of the orc complex at the origin of replication
## 165                          chromatin modifications during the maternal to zygotic transition mzt
## 330                                    ercc6 csb and ehmt2 g9a positively regulate rrna expression
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 467             7.467982e-35                        1         56       92
## 283             1.590650e-31                        1         44       63
## 1126            2.969744e-30                        1         44       66
## 191             3.474557e-30                        1         46       72
## 13              2.531680e-29                        1         43       65
## 828             2.746975e-29                        1         45       71
## 607             3.315912e-29                        1         49       84
## 87              1.620033e-28                        1         43       67
## 165             1.391507e-27                        1         43       69
## 330             4.268360e-27                        1         44       74
##               FDR
## 467  9.902545e-32
## 283  1.054601e-28
## 1126 1.151816e-27
## 191  1.151816e-27
## 13   6.070815e-27
## 828  6.070815e-27
## 607  6.281284e-27
## 87   2.685204e-26
## 165  2.050153e-25
## 330  5.659845e-25
## 
## $go_bp
##                                                   category
## 2553                               nucleosome organization
## 3484   protein localization to cenp a containing chromatin
## 3450                          protein dna complex assembly
## 3487 protein localization to chromosome centromeric region
## 199      attachment of spindle microtubules to kinetochore
## 4885                          sister chromatid segregation
## 2184  negative regulation of megakaryocyte differentiation
## 624                                 chromosome segregation
## 3763             regulation of cell cycle phase transition
## 3811                  regulation of chromosome segregation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 2553            1.960784e-16                        1         45      124
## 3484            1.231137e-13                        1         15       18
## 3450            3.393736e-13                        1         56      213
## 3487            4.508414e-12                        1         21       40
## 199             7.987326e-10                        1         21       49
## 4885            2.873941e-09                        1         51      225
## 2184            4.100465e-09                        1         12       18
## 624             5.219533e-09                        1         78      420
## 3763            9.010007e-09                        1         76      412
## 3811            9.772371e-09                        1         34      125
##               FDR
## 2553 1.042549e-12
## 3484 3.272978e-10
## 3450 6.014832e-10
## 3487 5.992809e-09
## 199  8.493722e-07
## 4885 2.546791e-06
## 2184 3.114596e-06
## 624  3.469032e-06
## 3763 5.195969e-06
## 3811 5.195969e-06
## 
## [1] "PrS_nor_GCM1_CE_down"
## $reactome
##                                   category over_represented_pvalue
## 1301         unfolded protein response upr            6.696299e-07
## 562         ire1alpha activates chaperones            3.020741e-06
## 630             metal ion slc transporters            3.595884e-05
## 1325                     zinc transporters            3.657054e-05
## 1309 vegfr2 mediated vascular permeability            4.496027e-05
## 1121                     signaling by vegf            4.582928e-05
## 1212                thyroxine biosynthesis            7.274400e-05
## 493         hsf1 dependent transactivation            1.125618e-04
## 270              diseases of glycosylation            1.503761e-04
## 225          cytosolic trna aminoacylation            3.217039e-04
##      under_represented_pvalue numDEInCat numInCat          FDR
## 1301                0.9999998         33       93 0.0008879293
## 562                 0.9999993         21       50 0.0020027515
## 630                 0.9999948         12       23 0.0101282702
## 1325                0.9999969          9       14 0.0101282702
## 1309                0.9999924         13       27 0.0101282702
## 1121                0.9999827         32      105 0.0101282702
## 1212                0.9999982          6        7 0.0137797918
## 493                 0.9999746         15       36 0.0186571231
## 270                 0.9999332         38      136 0.0221554183
## 225                 0.9999406         11       24 0.0392703761
## 
## $go_bp
##                                                                               category
## 1425 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
## 560                   cellular response to vascular endothelial growth factor stimulus
## 4612                                          response to endoplasmic reticulum stress
## 1680                                                  mesenchymal cell differentiation
## 4540                                                       regulation of wound healing
## 1421                                             intrinsic apoptotic signaling pathway
## 4722                                       response to topologically incorrect protein
## 1687                                                            mesenchyme development
## 954                                               epithelial to mesenchymal transition
## 1867                                                       muscle cell differentiation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 1425            6.707480e-07                0.9999998         24       60
## 560             1.101408e-06                0.9999997         24       61
## 4612            5.270650e-06                0.9999978         62      255
## 1680            5.329970e-06                0.9999976         60      240
## 4540            8.446621e-06                0.9999969         35      117
## 1421            9.492179e-06                0.9999953         69      297
## 4722            1.037098e-05                0.9999958         42      155
## 1687            1.674066e-05                0.9999916         69      297
## 954             2.034271e-05                0.9999913         43      161
## 1867            2.771449e-05                0.9999848         82      374
##              FDR
## 1425 0.002928094
## 560  0.002928094
## 4612 0.007084863
## 1680 0.007084863
## 4540 0.007877503
## 1421 0.007877503
## 4722 0.007877503
## 1687 0.011126261
## 954  0.012018020
## 1867 0.014735792
## 
## [1] "PrS_nor_GCM1_KO_up"
## $reactome
##                                                                                           category
## 467                                                                     hdacs deacetylate histones
## 283                                                                                dna methylation
## 191                                                           condensation of prophase chromosomes
## 1126                                                    sirt1 negatively regulates rrna expression
## 828                                                               prc2 methylates histones and dna
## 13   activated pkn1 stimulates transcription of ar androgen receptor regulated genes klk2 and klk3
## 157                                                                            cellular senescence
## 87                                        assembly of the orc complex at the origin of replication
## 758                                                            oxidative stress induced senescence
## 165                          chromatin modifications during the maternal to zygotic transition mzt
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 467             1.972722e-31                        1         50       92
## 283             1.879015e-30                        1         41       63
## 191             1.577704e-29                        1         43       72
## 1126            2.403441e-29                        1         41       66
## 828             1.385737e-28                        1         42       71
## 13              2.296409e-28                        1         40       65
## 157             1.033815e-27                        1         69      194
## 87              1.192736e-27                        1         40       67
## 758             1.574478e-27                        1         54      122
## 165             8.599933e-27                        1         40       69
##               FDR
## 467  2.615829e-28
## 283  1.245787e-27
## 191  6.973453e-27
## 1126 7.967407e-27
## 828  3.674975e-26
## 13   5.075064e-26
## 157  1.958341e-25
## 87   1.976960e-25
## 758  2.319732e-25
## 165  1.140351e-24
## 
## $go_bp
##                                                   category
## 2553                               nucleosome organization
## 3450                          protein dna complex assembly
## 3484   protein localization to cenp a containing chromatin
## 3487 protein localization to chromosome centromeric region
## 2184  negative regulation of megakaryocyte differentiation
## 2592                                     organelle fission
## 4885                          sister chromatid segregation
## 3811                  regulation of chromosome segregation
## 4090           regulation of megakaryocyte differentiation
## 1789                              mitotic nuclear division
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 2553            5.195964e-18                1.0000000         43      124
## 3450            1.106062e-13                1.0000000         51      213
## 3484            2.997629e-13                1.0000000         14       18
## 3487            1.323141e-12                1.0000000         20       40
## 2184            8.944542e-09                1.0000000         11       18
## 2592            1.021363e-08                1.0000000         72      461
## 4885            3.638216e-08                1.0000000         43      225
## 3811            7.897609e-08                1.0000000         29      125
## 4090            1.776750e-07                1.0000000         14       36
## 1789            2.614751e-07                0.9999999         47      273
##               FDR
## 2553 2.762694e-14
## 3450 2.940466e-10
## 3484 5.312798e-10
## 3487 1.758786e-09
## 2184 9.050974e-06
## 2592 9.050974e-06
## 4885 2.763485e-05
## 3811 5.248948e-05
## 4090 1.049665e-04
## 1789 1.368058e-04
## 
## [1] "PrS_nor_GCM1_KO_down"
## $reactome
##                                                                             category
## 630                                                       metal ion slc transporters
## 1325                                                               zinc transporters
## 270                                                        diseases of glycosylation
## 1200 tfap2 ap 2 family regulates transcription of growth factors and their receptors
## 1121                                                               signaling by vegf
## 263                            diseases associated with glycosaminoglycan metabolism
## 93                                                              attachment and entry
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 630             3.535974e-05                0.9999951         11       23
## 1325            8.008108e-05                0.9999927          8       14
## 270             9.946459e-05                0.9999585         34      136
## 1200            1.369956e-04                0.9999857          8       15
## 1121            1.567498e-04                0.9999403         27      105
## 263             1.787301e-04                0.9999586         14       38
## 93              2.626798e-04                0.9999625          9       19
##             FDR
## 630  0.03949936
## 1325 0.03949936
## 270  0.03949936
## 1200 0.03949936
## 1121 0.03949936
## 263  0.03949936
## 93   0.04975905
## 
## $go_bp
##                                                                               category
## 4269                                    regulation of polysaccharide metabolic process
## 2774                                                  polysaccharide metabolic process
## 1425 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
## 371                                                              cartilage development
## 560                   cellular response to vascular endothelial growth factor stimulus
## 612                                                        chondrocyte differentiation
## 659                                                      connective tissue development
## 2108                                                     negative regulation of growth
## 2376                                                  negative regulation of transport
## 4050                                             regulation of leukocyte proliferation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 4269            1.125419e-06                0.9999998         17       40
## 2774            3.300126e-06                0.9999990         27       90
## 1425            8.325300e-06                0.9999980         20       60
## 371             1.203553e-05                0.9999949         43      188
## 560             1.288100e-05                0.9999967         20       61
## 612             1.514156e-05                0.9999947         30      114
## 659             1.581880e-05                0.9999926         55      263
## 2108            1.665980e-05                0.9999925         49      230
## 2376            2.311529e-05                0.9999877         72      383
## 4050            2.367817e-05                0.9999893         47      219
##              FDR
## 4269 0.005983854
## 2774 0.008773384
## 1425 0.011072518
## 371  0.011072518
## 560  0.011072518
## 612  0.011072518
## 659  0.011072518
## 2108 0.011072518
## 2376 0.012057352
## 4050 0.012057352
## 
## [1] "PrS_nor_GCM1_PTC_up"
## $reactome
##                                                                                           category
## 467                                                                     hdacs deacetylate histones
## 283                                                                                dna methylation
## 828                                                               prc2 methylates histones and dna
## 191                                                           condensation of prophase chromosomes
## 758                                                            oxidative stress induced senescence
## 13   activated pkn1 stimulates transcription of ar androgen receptor regulated genes klk2 and klk3
## 1126                                                    sirt1 negatively regulates rrna expression
## 87                                        assembly of the orc complex at the origin of replication
## 157                                                                            cellular senescence
## 1043                                                senescence associated secretory phenotype sasp
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 467             1.465736e-27                        1         44       92
## 283             2.188595e-26                        1         36       63
## 828             5.080876e-25                        1         37       71
## 191             8.734610e-25                        1         37       72
## 758             1.116688e-24                        1         48      122
## 13              1.590379e-24                        1         35       65
## 1126            2.710157e-24                        1         35       66
## 87              5.985216e-24                        1         35       67
## 157             6.521321e-24                        1         60      194
## 1043            1.899892e-23                        1         44      110
##               FDR
## 467  1.943566e-24
## 283  1.451039e-23
## 828  2.245747e-22
## 191  2.895523e-22
## 758  2.961457e-22
## 13   3.514737e-22
## 1126 5.133812e-22
## 87   9.608080e-22
## 157  9.608080e-22
## 1043 2.519256e-21
## 
## $go_bp
##                                                   category
## 2553                               nucleosome organization
## 3484   protein localization to cenp a containing chromatin
## 3450                          protein dna complex assembly
## 3487 protein localization to chromosome centromeric region
## 2184  negative regulation of megakaryocyte differentiation
## 4090           regulation of megakaryocyte differentiation
## 3485                     protein localization to chromatin
## 4161            regulation of myeloid cell differentiation
## 5087                                 telomere organization
## 2213   negative regulation of myeloid cell differentiation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 2553            5.094182e-17                1.0000000         39      124
## 3484            5.520787e-16                1.0000000         15       18
## 3450            1.072808e-13                1.0000000         47      213
## 3487            1.355066e-11                1.0000000         18       40
## 2184            6.666303e-11                1.0000000         12       18
## 4090            2.731074e-09                1.0000000         15       36
## 3485            7.851264e-09                1.0000000         19       59
## 4161            1.489780e-08                1.0000000         36      187
## 5087            9.548740e-08                1.0000000         34      187
## 2213            5.596545e-07                0.9999999         20       83
##               FDR
## 2553 2.708577e-13
## 3484 1.467701e-12
## 3450 1.901373e-10
## 3487 1.801222e-08
## 2184 7.088946e-08
## 4090 2.420187e-06
## 3485 5.963596e-06
## 4161 9.901451e-06
## 5087 5.641184e-05
## 2213 2.975683e-04
## 
## [1] "PrS_nor_GCM1_PTC_down"
## $reactome
##                                                                             category
## 630                                                       metal ion slc transporters
## 1325                                                               zinc transporters
## 1200 tfap2 ap 2 family regulates transcription of growth factors and their receptors
## 774                                                     peptide hormone biosynthesis
## 1121                                                               signaling by vegf
## 263                            diseases associated with glycosaminoglycan metabolism
## 1118                                                signaling by tgfb family members
## 270                                                        diseases of glycosylation
## 93                                                              attachment and entry
## 1301                                                   unfolded protein response upr
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 630             4.028729e-05                0.9999943         11       23
## 1325            8.924555e-05                0.9999917          8       14
## 1200            1.547397e-04                0.9999835          8       15
## 774             1.883732e-04                0.9999840          7       12
## 1121            1.916607e-04                0.9999260         27      105
## 263             1.918146e-04                0.9999553         14       38
## 1118            2.366128e-04                0.9999018         30      122
## 270             2.667070e-04                0.9998833         33      136
## 93              2.751037e-04                0.9999604          9       19
## 1301            3.330896e-04                0.9998745         24       93
##             FDR
## 630  0.04053195
## 1325 0.04053195
## 1200 0.04053195
## 774  0.04053195
## 1121 0.04053195
## 263  0.04053195
## 1118 0.04053195
## 270  0.04053195
## 93   0.04053195
## 1301 0.04399558
## 
## $go_bp
##                                                                               category
## 254                                                      biomineral tissue development
## 560                   cellular response to vascular endothelial growth factor stimulus
## 4269                                    regulation of polysaccharide metabolic process
## 1425 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
## 2774                                                  polysaccharide metabolic process
## 1680                                                  mesenchymal cell differentiation
## 612                                                        chondrocyte differentiation
## 611                                                            chondrocyte development
## 5308                                                                     wound healing
## 1867                                                       muscle cell differentiation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 254             3.638446e-07                0.9999999         42      158
## 560             9.797003e-07                0.9999998         22       61
## 4269            1.382109e-06                0.9999998         17       40
## 1425            2.689562e-06                0.9999994         21       60
## 2774            4.364221e-06                0.9999987         27       90
## 1680            6.254918e-06                0.9999973         53      240
## 612             6.945796e-06                0.9999976         31      114
## 611             7.828736e-06                0.9999987         14       32
## 5308            7.947119e-06                0.9999961         76      389
## 1867            7.949952e-06                0.9999961         74      374
##              FDR
## 254  0.001934562
## 560  0.002449559
## 4269 0.002449559
## 1425 0.003575101
## 2774 0.004226989
## 1680 0.004226989
## 612  0.004226989
## 611  0.004226989
## 5308 0.004226989
## 1867 0.004226989
## 
## [1] "PrS_nor_FOSB_KO_up"
## $reactome
##                                                         category
## 518                           integrin cell surface interactions
## 346                            extracellular matrix organization
## 185                                         collagen degradation
## 85  assembly of collagen fibrils and other multimeric structures
## 184                                 collagen chain trimerization
## 186                                           collagen formation
## 183                  collagen biosynthesis and modifying enzymes
## 307                                            ecm proteoglycans
## 40                               adherens junctions interactions
## 253                      degradation of the extracellular matrix
##     over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 518            1.656022e-08                1.0000000         10       78
## 346            3.431410e-08                1.0000000         17      285
## 185            5.401527e-07                1.0000000          8       60
## 85             6.310812e-07                1.0000000          8       60
## 184            6.873574e-07                1.0000000          7       42
## 186            1.044059e-06                0.9999999          9       88
## 183            1.169812e-06                0.9999999          8       65
## 307            3.281918e-06                0.9999997          8       75
## 40             4.041532e-06                0.9999997          7       53
## 253            4.337458e-06                0.9999995         10      134
##              FDR
## 518 2.195885e-05
## 346 2.275025e-05
## 185 1.822872e-04
## 85  1.822872e-04
## 184 1.822872e-04
## 186 2.215958e-04
## 183 2.215958e-04
## 307 5.439778e-04
## 40  5.751469e-04
## 253 5.751469e-04
## 
## $go_bp
##                                           category over_represented_pvalue
## 645                   collagen fibril organization            3.354659e-10
## 1022 external encapsulating structure organization            2.492030e-09
## 371                          cartilage development            3.236358e-07
## 82                   ameboidal type cell migration            3.520497e-07
## 659                  connective tissue development            6.059314e-07
## 612                    chondrocyte differentiation            9.895230e-07
## 322                canonical wnt signaling pathway            2.037041e-06
## 1687                        mesenchyme development            2.729083e-06
## 1239                           heart morphogenesis            3.501847e-06
## 4997          striated muscle cell differentiation            4.598044e-06
##      under_represented_pvalue numDEInCat numInCat          FDR
## 645                 1.0000000         11       63 1.783672e-06
## 1022                1.0000000         19      302 6.625063e-06
## 371                 1.0000000         13      188 4.679621e-04
## 82                  0.9999999         19      415 4.679621e-04
## 659                 0.9999999         15      263 6.443475e-04
## 612                 0.9999999         10      114 8.768823e-04
## 322                 0.9999996         15      295 1.547278e-03
## 1687                0.9999995         15      297 1.813817e-03
## 1239                0.9999994         14      255 2.068814e-03
## 4997                0.9999991         14      274 2.243809e-03
## 
## [1] "PrS_nor_FOSB_PTC_up"
## $reactome
##                                                          category
## 346                             extracellular matrix organization
## 518                            integrin cell surface interactions
## 307                                             ecm proteoglycans
## 183                   collagen biosynthesis and modifying enzymes
## 184                                  collagen chain trimerization
## 253                       degradation of the extracellular matrix
## 185                                          collagen degradation
## 186                                            collagen formation
## 85   assembly of collagen fibrils and other multimeric structures
## 1163                                        syndecan interactions
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 346             1.436869e-11                1.0000000         29      285
## 518             1.755802e-09                1.0000000         14       78
## 307             2.243631e-08                1.0000000         13       75
## 183             4.031943e-08                1.0000000         12       65
## 184             4.467943e-08                1.0000000         10       42
## 253             9.915951e-08                1.0000000         16      134
## 185             1.356254e-07                1.0000000         11       60
## 186             1.464910e-07                1.0000000         13       88
## 85              1.620152e-06                0.9999998         10       60
## 1163            3.499459e-06                0.9999998          7       27
##               FDR
## 346  1.905289e-08
## 518  1.164097e-06
## 307  9.916849e-06
## 183  1.184899e-05
## 184  1.184899e-05
## 253  2.191425e-05
## 185  2.428089e-05
## 186  2.428089e-05
## 85   2.387024e-04
## 1163 4.640283e-04
## 
## $go_bp
##                                           category over_represented_pvalue
## 1022 external encapsulating structure organization            1.925057e-14
## 1239                           heart morphogenesis            1.519626e-13
## 645                   collagen fibril organization            1.967602e-12
## 1687                        mesenchyme development            1.713638e-11
## 659                  connective tissue development            2.538679e-11
## 371                          cartilage development            6.821165e-11
## 1877                     muscle tissue development            8.150329e-11
## 5000            striated muscle tissue development            9.504090e-11
## 82                   ameboidal type cell migration            4.903542e-10
## 1680              mesenchymal cell differentiation            5.439706e-10
##      under_represented_pvalue numDEInCat numInCat          FDR
## 1022                        1         34      302 1.023553e-10
## 1239                        1         31      255 4.039925e-10
## 645                         1         16       63 3.487247e-09
## 1687                        1         30      297 2.277853e-08
## 659                         1         28      263 2.699632e-08
## 371                         1         23      188 6.044689e-08
## 1877                        1         34      400 6.190757e-08
## 5000                        1         26      241 6.316656e-08
## 82                          1         33      415 2.892291e-07
## 1680                        1         25      240 2.892291e-07
## 
## [1] "PrS_nor_FOSB_PTC_down"
## $reactome
##                                          category over_represented_pvalue
## 762          p75 ntr receptor mediated signalling            1.338713e-05
## 148 cell death signalling via nrage nrif and nade            3.781977e-05
## 399               g alpha 12 13 signalling events            4.948099e-05
## 725               nrage signals death through jnk            1.312017e-04
##     under_represented_pvalue numDEInCat numInCat        FDR
## 762                0.9999989          7       97 0.01775133
## 148                0.9999971          6       76 0.02187060
## 399                0.9999960          6       80 0.02187060
## 725                0.9999907          5       59 0.04349338
## 
## [1] "PrS_nor_EPAS1_CE_up"
## $reactome
##                        category over_represented_pvalue
## 277  dissolution of fibrin clot            2.198485e-05
## 618 metabolism of carbohydrates            5.363641e-05
##     under_represented_pvalue numDEInCat numInCat        FDR
## 277                0.9999991          5       13 0.02915191
## 618                0.9999822         22      284 0.03556094
## 
## $go_bp
##                                          category over_represented_pvalue
## 1055                 fatty acid metabolic process            3.613651e-06
## 488  cellular response to decreased oxygen levels            6.688351e-06
## 1421        intrinsic apoptotic signaling pathway            7.550311e-06
## 1167                    glucose metabolic process            1.379079e-05
## 499               cellular response to fatty acid            1.400568e-05
## 4619                       response to fatty acid            1.535808e-05
## 3613                   pyruvate metabolic process            1.586226e-05
## 531            cellular response to oxygen levels            2.041856e-05
## 1827             monosaccharide metabolic process            2.666690e-05
## 2753                       plasminogen activation            3.111105e-05
##      under_represented_pvalue numDEInCat numInCat        FDR
## 1055                0.9999988         27      352 0.01204852
## 488                 0.9999985         16      142 0.01204852
## 1421                0.9999976         24      297 0.01204852
## 1167                0.9999966         17      174 0.01204852
## 499                 0.9999989          7       29 0.01204852
## 4619                0.9999981          9       50 0.01204852
## 3613                0.9999969         13      108 0.01204852
## 531                 0.9999950         16      156 0.01357069
## 1827                0.9999920         20      241 0.01571608
## 2753                0.9999979          6       23 0.01571608
## 
## [1] "PrS_nor_EPAS1_CE_down"
## $reactome
##                                                                                           category
## 13   activated pkn1 stimulates transcription of ar androgen receptor regulated genes klk2 and klk3
## 191                                                           condensation of prophase chromosomes
## 467                                                                     hdacs deacetylate histones
## 1043                                                senescence associated secretory phenotype sasp
## 829                                                            pre notch expression and processing
## 466                                                                               hcmv late events
## 986                                                               rmts methylate histone arginines
## 606                                                                                        meiosis
## 608                                                                               meiotic synapsis
## 283                                                                                dna methylation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 13              1.595702e-06                0.9999999          9       65
## 191             4.361946e-06                0.9999995          9       72
## 467             4.562914e-06                0.9999994         10       92
## 1043            4.630293e-06                0.9999993         11      110
## 829             4.796600e-06                0.9999993         11      107
## 466             6.814211e-06                0.9999990         11      114
## 986             8.902286e-06                0.9999990          9       76
## 606             1.150517e-05                0.9999982         11      114
## 608             1.230217e-05                0.9999985          9       75
## 283             1.257684e-05                0.9999987          8       63
##              FDR
## 13   0.001272058
## 191  0.001272058
## 467  0.001272058
## 1043 0.001272058
## 829  0.001272058
## 466  0.001505941
## 986  0.001667688
## 606  0.001667688
## 608  0.001667688
## 283  0.001667688
## 
## [1] "PrS_nor_EPAS1_PTC_up"
## $reactome
##                       category over_represented_pvalue under_represented_pvalue
## 277 dissolution of fibrin clot            1.196543e-05                0.9999999
##     numDEInCat numInCat        FDR
## 277          3       13 0.01586616
## 
## $go_bp
##                                                     category
## 2753                                  plasminogen activation
## 5308                                           wound healing
## 4352 regulation of release of cytochrome c from mitochondria
## 3930                              regulation of fibrinolysis
## 1531                        liposaccharide metabolic process
## 4263                    regulation of plasminogen activation
## 5317                                      zymogen activation
## 4545               release of cytochrome c from mitochondria
## 2016          negative regulation of cell substrate adhesion
## 4540                             regulation of wound healing
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 2753            1.171197e-06                1.0000000          4       23
## 5308            7.274508e-06                0.9999992          9      389
## 4352            1.549539e-05                0.9999996          4       43
## 3930            2.743100e-05                0.9999997          3       17
## 1531            2.899217e-05                0.9999985          5      102
## 4263            3.289378e-05                0.9999996          3       18
## 5317            3.309511e-05                0.9999990          4       52
## 4545            3.857676e-05                0.9999987          4       54
## 2016            4.024798e-05                0.9999987          4       55
## 4540            5.490820e-05                0.9999968          5      117
##              FDR
## 2753 0.006227254
## 5308 0.019339280
## 4352 0.023777610
## 3930 0.023777610
## 1531 0.023777610
## 4263 0.023777610
## 5317 0.023777610
## 4545 0.023777610
## 2016 0.023777610
## 4540 0.029194690
## 
## [1] "PrS_nor_GRHL1_CE_up"
## $reactome
##                            category over_represented_pvalue
## 525 interferon alpha beta signaling            2.262603e-10
## 526      interferon gamma signaling            2.184318e-07
## 527            interferon signaling            3.661905e-07
## 184    collagen chain trimerization            8.682218e-05
## 307               ecm proteoglycans            1.229151e-04
##     under_represented_pvalue numDEInCat numInCat          FDR
## 525                1.0000000         18       65 3.000212e-07
## 526                1.0000000         16       81 1.448203e-04
## 527                0.9999999         29      242 1.618562e-04
## 184                0.9999869          9       42 2.878155e-02
## 307                0.9999731         12       75 3.259707e-02
## 
## $go_bp
##                                             category over_represented_pvalue
## 2397 negative regulation of viral genome replication            4.301158e-08
## 4644                     response to interferon beta            1.591006e-07
## 513             cellular response to interferon beta            1.932150e-07
## 2400            negative regulation of viral process            4.248355e-07
## 4727                   response to type i interferon            9.094625e-07
## 1374           interferon mediated signaling pathway            1.127029e-06
## 4901                smad protein signal transduction            1.388827e-06
## 717                     defense response to symbiont            3.844608e-06
## 1687                          mesenchyme development            1.006543e-05
## 4734                               response to virus            1.403765e-05
##      under_represented_pvalue numDEInCat numInCat          FDR
## 2397                1.0000000         14       52 0.0002286926
## 4644                1.0000000         10       31 0.0003424413
## 513                 1.0000000          9       24 0.0003424413
## 2400                0.9999999         16       81 0.0005647125
## 4727                0.9999998         15       74 0.0009671225
## 1374                0.9999998         16       87 0.0009987356
## 4901                0.9999998         15       75 0.0010549134
## 717                 0.9999987         31      289 0.0025552229
## 1687                0.9999963         31      297 0.0059464333
## 4734                0.9999944         35      375 0.0074638180
## 
## [1] "PrS_nor_GRHL1_CE_down"
## $reactome
##                                                                             category
## 80                                                 asparagine n linked glycosylation
## 493                                                   hsf1 dependent transactivation
## 1301                                                   unfolded protein response upr
## 1200 tfap2 ap 2 family regulates transcription of growth factors and their receptors
## 562                                                   ire1alpha activates chaperones
## 774                                                     peptide hormone biosynthesis
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 80              1.302512e-05                0.9999942         47      300
## 493             2.373316e-05                0.9999961         12       36
## 1301            6.369956e-05                0.9999807         20       93
## 1200            8.902948e-05                0.9999922          7       15
## 562             1.516482e-04                0.9999653         13       50
## 774             1.853290e-04                0.9999861          6       12
##             FDR
## 80   0.01573509
## 493  0.01573509
## 1301 0.02815520
## 1200 0.02951327
## 562  0.04021711
## 774  0.04095770
## 
## $go_bp
##                                      category over_represented_pvalue
## 4612 response to endoplasmic reticulum stress            2.119732e-07
## 963                              erad pathway            2.749650e-06
## 885               endocrine hormone secretion            3.203522e-06
## 477      cellular response to biotic stimulus            4.607135e-06
## 1299                        hormone transport            7.020740e-06
## 3482   protein localization to cell periphery            8.115957e-06
## 4642                      response to insulin            9.500709e-06
## 3536                        protein refolding            1.147332e-05
## 3510  protein localization to plasma membrane            1.259720e-05
## 3690                  regulation of autophagy            1.379981e-05
##      under_represented_pvalue numDEInCat numInCat         FDR
## 4612                0.9999999         45      255 0.001127061
## 963                 0.9999992         24      108 0.005677709
## 885                 0.9999994         16       54 0.005677709
## 477                 0.9999982         37      211 0.006124035
## 1299                0.9999970         46      292 0.007192091
## 3482                0.9999964         51      341 0.007192091
## 4642                0.9999961         40      244 0.007216467
## 3536                0.9999987         10       25 0.007337361
## 3510                0.9999945         44      283 0.007337361
## 3690                0.9999937         50      341 0.007337361
## 
## [1] "PrS_nor_GRHL1_KO_up"
## $reactome
##                                        category over_represented_pvalue
## 525             interferon alpha beta signaling            3.890682e-11
## 184                collagen chain trimerization            6.021122e-07
## 183 collagen biosynthesis and modifying enzymes            1.504942e-06
## 527                        interferon signaling            5.177422e-06
## 346           extracellular matrix organization            2.091641e-05
## 518          integrin cell surface interactions            3.927685e-05
## 307                           ecm proteoglycans            4.501624e-05
## 186                          collagen formation            4.629615e-05
## 526                  interferon gamma signaling            4.890721e-05
## 185                        collagen degradation            1.132855e-04
##     under_represented_pvalue numDEInCat numInCat          FDR
## 525                1.0000000         18       65 5.159045e-08
## 184                0.9999999         11       42 3.992004e-04
## 183                0.9999998         13       65 6.651844e-04
## 527                0.9999984         25      242 1.716315e-03
## 346                0.9999926         27      285 5.547032e-03
## 518                0.9999924         12       78 7.205663e-03
## 307                0.9999912         12       75 7.205663e-03
## 186                0.9999901         13       88 7.205663e-03
## 526                0.9999902         12       81 7.205663e-03
## 185                0.9999796         10       60 1.502165e-02
## 
## $go_bp
##                                                                      category
## 2397                          negative regulation of viral genome replication
## 4901                                         smad protein signal transduction
## 2400                                     negative regulation of viral process
## 1687                                                   mesenchyme development
## 4727                                            response to type i interferon
## 1374                                    interferon mediated signaling pathway
## 5158 transmembrane receptor protein serine threonine kinase signaling pathway
## 1870                                                muscle cell proliferation
## 2166                                        negative regulation of locomotion
## 1680                                         mesenchymal cell differentiation
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 2397            8.686401e-09                1.0000000         14       52
## 4901            2.550998e-07                1.0000000         15       75
## 2400            4.212869e-07                0.9999999         15       81
## 1687            5.509640e-07                0.9999998         31      297
## 4727            1.038527e-06                0.9999998         14       74
## 1374            1.058408e-06                0.9999998         15       87
## 5158            1.076901e-06                0.9999996         35      359
## 1870            1.329007e-06                0.9999996         23      191
## 2166            2.022586e-06                0.9999993         31      315
## 1680            2.438094e-06                0.9999993         26      240
##               FDR
## 2397 4.618559e-05
## 4901 6.781829e-04
## 2400 7.323689e-04
## 1687 7.323689e-04
## 4727 8.179833e-04
## 1374 8.179833e-04
## 5158 8.179833e-04
## 1870 8.832911e-04
## 2166 1.194899e-03
## 1680 1.296335e-03
## 
## [1] "PrS_nor_GRHL1_KO_down"
## $go_bp
##                                         category over_represented_pvalue
## 3372        positive regulation of wound healing            3.374043e-07
## 3261 positive regulation of response to wounding            6.796705e-07
## 4873                              signal release            1.186191e-05
## 1668            membrane lipid metabolic process            2.258557e-05
## 1299                           hormone transport            2.892334e-05
## 4722 response to topologically incorrect protein            3.476257e-05
## 2719              phospholipid metabolic process            3.568355e-05
## 1018                                  exocytosis            5.470721e-05
## 5308                               wound healing            6.424330e-05
## 477         cellular response to biotic stimulus            7.715935e-05
##      under_represented_pvalue numDEInCat numInCat         FDR
## 3372                1.0000000         14       56 0.001793978
## 3261                0.9999999         15       68 0.001806904
## 4873                0.9999948         43      446 0.021023267
## 1668                0.9999925         24      199 0.027104204
## 1299                0.9999887         31      292 0.027104204
## 4722                0.9999895         20      155 0.027104204
## 2719                0.9999850         35      359 0.027104204
## 1018                0.9999771         33      331 0.036359777
## 5308                0.9999714         37      389 0.037953515
## 477                 0.9999722         24      211 0.041025627
## 
## [1] "PrS_nor_GRHL1_PTC_up"
## $reactome
##                                    category over_represented_pvalue
## 710  non integrin membrane ecm interactions            7.148400e-10
## 518      integrin cell surface interactions            6.852697e-08
## 958                    rho gtpase effectors            2.075012e-07
## 307                       ecm proteoglycans            2.652440e-07
## 960            rho gtpases activate formins            9.592101e-07
## 1163                  syndecan interactions            1.007292e-06
## 346       extracellular matrix organization            3.722419e-06
## 957                        rho gtpase cycle            6.683154e-06
## 1131              smooth muscle contraction            1.189650e-05
## 1042                semaphorin interactions            1.835703e-05
##      under_represented_pvalue numDEInCat numInCat          FDR
## 710                 1.0000000         24       58 9.478779e-07
## 518                 1.0000000         25       78 4.543338e-05
## 958                 1.0000000         58      316 8.792838e-05
## 307                 0.9999999         24       75 8.792838e-05
## 960                 0.9999997         32      136 2.226116e-04
## 1163                0.9999999         13       27 2.226116e-04
## 346                 0.9999985         54      285 7.051324e-04
## 957                 0.9999966         75      450 1.107733e-03
## 1131                0.9999977         15       43 1.752751e-03
## 1042                0.9999955         18       63 2.279380e-03
## 
## $go_bp
##                                     category over_represented_pvalue
## 82             ameboidal type cell migration            5.669079e-11
## 38         actomyosin structure organization            1.916489e-10
## 5308                           wound healing            3.273662e-10
## 18               actin filament organization            3.986723e-10
## 5112                        tissue migration            7.685190e-09
## 16        actin filament bundle organization            3.698749e-08
## 4209          regulation of nuclear division            8.161009e-08
## 4132  regulation of mitotic nuclear division            1.461424e-07
## 1687                  mesenchyme development            1.848023e-07
## 2234 negative regulation of nuclear division            2.618742e-07
##      under_represented_pvalue numDEInCat numInCat          FDR
## 82                  1.0000000         85      415 3.014249e-07
## 38                  1.0000000         51      200 5.094987e-07
## 5308                1.0000000         79      389 5.299352e-07
## 18                  1.0000000         86      441 5.299352e-07
## 5112                1.0000000         63      300 8.172431e-06
## 16                  1.0000000         40      158 3.277708e-05
## 4209                1.0000000         34      136 6.198870e-05
## 4132                1.0000000         30      115 9.712992e-05
## 1687                1.0000000         59      297 1.091771e-04
## 2234                0.9999999         20       61 1.392385e-04
## 
## [1] "PrS_nor_GRHL1_PTC_down"
## $reactome
##                                                                             category
## 1301                                                   unfolded protein response upr
## 80                                                 asparagine n linked glycosylation
## 562                                                   ire1alpha activates chaperones
## 91                                         atf6 atf6 alpha activates chaperone genes
## 1200 tfap2 ap 2 family regulates transcription of growth factors and their receptors
## 947                                       response of eif2ak1 hri to heme deficiency
## 92                                              atf6 atf6 alpha activates chaperones
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 1301            1.036660e-07                1.0000000         31       93
## 80              2.254689e-06                0.9999991         65      300
## 562             3.077659e-06                0.9999994         19       50
## 91              4.951005e-05                0.9999973          7       10
## 1200            1.433777e-04                0.9999849          8       15
## 947             1.552943e-04                0.9999835          8       15
## 92              2.517765e-04                0.9999775          7       12
##               FDR
## 1301 0.0001374611
## 80   0.0013603254
## 562  0.0013603254
## 91   0.0164125812
## 1200 0.0343200368
## 947  0.0343200368
## 92   0.0476936605
## 
## $go_bp
##                                              category over_represented_pvalue
## 4612         response to endoplasmic reticulum stress            1.852016e-08
## 3494    protein localization to endoplasmic reticulum            6.279844e-08
## 3216 positive regulation of protein catabolic process            1.656429e-07
## 4642                              response to insulin            1.167749e-06
## 1299                                hormone transport            2.736726e-06
## 887                                 endocrine process            4.469054e-06
## 3452          protein exit from endoplasmic reticulum            4.626179e-06
## 4697                      response to peptide hormone            6.166372e-06
## 963                                      erad pathway            1.228118e-05
## 477              cellular response to biotic stimulus            1.234294e-05
##      under_represented_pvalue numDEInCat numInCat          FDR
## 4612                1.0000000         61      255 9.847171e-05
## 3494                1.0000000         26       72 1.669497e-04
## 3216                1.0000000         50      204 2.935744e-04
## 4642                0.9999996         55      244 1.552230e-03
## 1299                0.9999989         62      292 2.910234e-03
## 887                 0.9999987         25       81 3.513913e-03
## 3452                0.9999990         18       49 3.513913e-03
## 4697                0.9999970         76      389 4.098325e-03
## 963                 0.9999958         29      108 6.024932e-03
## 477                 0.9999946         47      211 6.024932e-03
## 
## [1] "PrS_hyp_EPAS1_CE_up"
## $reactome
##                                             category over_represented_pvalue
## 56                       amino acids regulate mtorc1            3.500350e-07
## 515                       insulin receptor recycling            1.967660e-06
## 1267           transferrin endocytosis and recycling            4.604666e-06
## 1301                   unfolded protein response upr            1.369721e-05
## 1121                               signaling by vegf            1.902357e-05
## 1006            ros and rns production in phagocytes            3.293891e-05
## 162                         cholesterol biosynthesis            5.099474e-05
## 55   amino acid transport across the plasma membrane            5.772631e-05
## 93                              attachment and entry            1.148130e-04
## 564                        iron uptake and transport            1.422465e-04
##      under_represented_pvalue numDEInCat numInCat          FDR
## 56                  0.9999999         20       54 0.0004641463
## 515                 0.9999998         13       28 0.0013045589
## 1267                0.9999994         13       30 0.0020352622
## 1301                0.9999958         25       93 0.0045406251
## 1121                0.9999937         27      105 0.0050450496
## 1006                0.9999940         13       35 0.0072794981
## 162                 0.9999921         11       27 0.0095681357
## 55                  0.9999899         12       31 0.0095681357
## 93                  0.9999854          9       19 0.0169157832
## 564                 0.9999623         16       55 0.0188618912
## 
## $go_bp
##                                                                               category
## 4612                                          response to endoplasmic reticulum stress
## 1578                                                                    macroautophagy
## 4078                                                      regulation of macroautophagy
## 5040                                              synaptic vesicle lumen acidification
## 3452                                           protein exit from endoplasmic reticulum
## 1425 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
## 5154                                                          translational initiation
## 4722                                       response to topologically incorrect protein
## 963                                                                       erad pathway
## 3690                                                           regulation of autophagy
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 4612            2.144110e-09                1.0000000         57      255
## 1578            1.146466e-07                1.0000000         63      327
## 4078            1.742118e-07                0.9999999         38      156
## 5040            2.408251e-07                1.0000000         10       16
## 3452            4.397676e-07                0.9999999         18       49
## 1425            6.792466e-07                0.9999999         20       60
## 5154            8.717581e-07                0.9999997         30      118
## 4722            8.741577e-07                0.9999997         36      155
## 963             1.521337e-06                0.9999996         28      108
## 3690            1.538510e-06                0.9999995         62      341
##               FDR
## 4612 1.140023e-05
## 1578 3.047880e-04
## 4078 3.087613e-04
## 5040 3.201167e-04
## 3452 4.676488e-04
## 1425 5.809870e-04
## 5154 5.809870e-04
## 4722 5.809870e-04
## 963  8.180257e-04
## 3690 8.180257e-04
## 
## [1] "PrS_hyp_EPAS1_CE_down"
## $go_bp
##                                                                category
## 214                                                       axon guidance
## 5240                             vascular process in circulatory system
## 1681                                         mesenchymal cell migration
## 2417                                  neural crest cell differentiation
## 2447 neuron projection extension involved in neuron projection guidance
## 1926                                                negative chemotaxis
## 2006                            negative regulation of cell development
## 462                      cellular modified amino acid metabolic process
## 2328                negative regulation of smooth muscle cell migration
## 4975                                              stem cell development
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 214             3.388209e-07                0.9999999         31      222
## 5240            4.660862e-06                0.9999984         31      245
## 1681            5.933271e-06                0.9999990         13       60
## 2417            9.159955e-06                0.9999980         16       91
## 2447            1.848098e-05                0.9999975         10       38
## 1926            1.981031e-05                0.9999969         11       47
## 2006            2.235815e-05                0.9999917         29      253
## 462             4.024245e-05                0.9999892         17      120
## 2328            6.991205e-05                0.9999932          7       22
## 4975            8.733168e-05                0.9999787         14       86
##              FDR
## 214  0.001801511
## 5240 0.010515733
## 1681 0.010515733
## 2417 0.012175870
## 2447 0.016982615
## 1926 0.016982615
## 2006 0.016982615
## 462  0.026746141
## 2328 0.041302487
## 4975 0.043010491
## 
## [1] "PrS_hyp_EPAS1_KO_up"
## $reactome
##                         category over_represented_pvalue
## 632 metallothioneins bind metals            2.148456e-05
##     under_represented_pvalue numDEInCat numInCat        FDR
## 632                0.9999994          5        8 0.02848853
## 
## $go_bp
##                                      category over_represented_pvalue
## 1521                   lipid import into cell            1.247918e-05
## 4612 response to endoplasmic reticulum stress            2.722863e-05
## 1417       intracellular zinc ion homeostasis            3.169932e-05
## 4050    regulation of leukocyte proliferation            3.624881e-05
## 4540              regulation of wound healing            5.140192e-05
## 18                actin filament organization            5.478638e-05
## 1997     negative regulation of cell adhesion            5.545999e-05
## 2376         negative regulation of transport            5.784322e-05
## 4693                response to oxygen levels            8.077530e-05
##      under_represented_pvalue numDEInCat numInCat        FDR
## 1521                0.9999989          8       20 0.03844405
## 4612                0.9999893         32      255 0.03844405
## 1417                0.9999960          9       30 0.03844405
## 4050                0.9999862         29      219 0.03844405
## 4540                0.9999848         19      117 0.03844405
## 18                  0.9999734         47      441 0.03844405
## 1997                0.9999772         32      260 0.03844405
## 2376                0.9999730         42      383 0.03844405
## 4693                0.9999637         37      320 0.04772025
## 
## [1] "PrS_hyp_EPAS1_KO_down"
## $reactome
##                                        category over_represented_pvalue
## 184                collagen chain trimerization            1.906102e-06
## 253     degradation of the extracellular matrix            4.166207e-06
## 185                        collagen degradation            5.201623e-06
## 183 collagen biosynthesis and modifying enzymes            7.172428e-05
## 186                          collagen formation            1.633145e-04
##     under_represented_pvalue numDEInCat numInCat         FDR
## 184                0.9999998          9       42 0.002299118
## 253                0.9999992         15      134 0.002299118
## 185                0.9999994         10       60 0.002299118
## 183                0.9999890          9       65 0.023776598
## 186                0.9999684         10       88 0.043310997
## 
## $go_bp
##                           category over_represented_pvalue
## 337    cardiac chamber development            5.854137e-08
## 214                  axon guidance            6.844080e-08
## 363  cardiac ventricle development            1.208774e-07
## 1681    mesenchymal cell migration            5.382602e-07
## 869    embryonic organ development            8.762555e-07
## 165        appendage morphogenesis            1.321765e-06
## 870  embryonic organ morphogenesis            2.184799e-06
## 4711     response to retinoic acid            3.660770e-06
## 4975         stem cell development            3.780786e-06
## 2567                 odontogenesis            5.439896e-06
##      under_represented_pvalue numDEInCat numInCat          FDR
## 337                 1.0000000         20      165 0.0001819499
## 214                 1.0000000         23      222 0.0001819499
## 363                 1.0000000         17      124 0.0002142351
## 1681                0.9999999         11       60 0.0007154824
## 869                 0.9999997         31      424 0.0009318101
## 165                 0.9999997         16      141 0.0011713043
## 870                 0.9999994         23      271 0.0016595106
## 4711                0.9999994         13       99 0.0022336041
## 4975                0.9999994         12       86 0.0022336041
## 2567                0.9999990         14      121 0.0026673520
## 
## [1] "PrS_hyp_EPAS1_PTC_up"
## $reactome
##                          category over_represented_pvalue
## 225 cytosolic trna aminoacylation             1.17005e-05
## 632  metallothioneins bind metals             2.79189e-05
##     under_represented_pvalue numDEInCat numInCat        FDR
## 225                0.9999988          9       24 0.01551486
## 632                0.9999992          5        8 0.01851023
## 
## $go_bp
##                                           category over_represented_pvalue
## 1417            intracellular zinc ion homeostasis            5.998904e-06
## 2599          organic acid transmembrane transport            6.465104e-06
## 98              amino acid transmembrane transport            6.881824e-06
## 4697                   response to peptide hormone            2.074831e-05
## 1459    l alpha amino acid transmembrane transport            2.858616e-05
## 2774              polysaccharide metabolic process            3.893557e-05
## 456              cellular ketone metabolic process            6.228389e-05
## 1159                      glucan metabolic process            6.996942e-05
## 924               energy reserve metabolic process            7.662500e-05
## 535  cellular response to peptide hormone stimulus            9.628083e-05
##      under_represented_pvalue numDEInCat numInCat        FDR
## 1417                0.9999993         10       30 0.01219689
## 2599                0.9999981         24      144 0.01219689
## 98                  0.9999984         18       91 0.01219689
## 4697                0.9999904         46      389 0.02757969
## 1459                0.9999939         14       66 0.03039853
## 2774                0.9999898         17       90 0.03450341
## 456                 0.9999765         27      198 0.04526835
## 1159                0.9999837         14       69 0.04526835
## 924                 0.9999808         15       77 0.04526835
## 535                 0.9999575         35      283 0.04948143
## 
## [1] "PrS_hyp_EPAS1_PTC_down"
## $reactome
##                                        category over_represented_pvalue
## 184                collagen chain trimerization            2.117636e-07
## 185                        collagen degradation            8.060941e-06
## 183 collagen biosynthesis and modifying enzymes            1.917716e-05
## 253     degradation of the extracellular matrix            9.615816e-05
##     under_represented_pvalue numDEInCat numInCat          FDR
## 184                1.0000000         11       42 0.0002807985
## 185                0.9999988         11       60 0.0053444036
## 183                0.9999969         11       65 0.0084763042
## 253                0.9999746         15      134 0.0318764295
## 
## $go_bp
##                                                    category
## 322                         canonical wnt signaling pathway
## 3732          regulation of canonical wnt signaling pathway
## 214                                           axon guidance
## 403                              cell cell signaling by wnt
## 2166                      negative regulation of locomotion
## 4175               regulation of nervous system development
## 4538                    regulation of wnt signaling pathway
## 1982 negative regulation of canonical wnt signaling pathway
## 2404           negative regulation of wnt signaling pathway
## 1681                             mesenchymal cell migration
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 322             5.542322e-08                1.0000000         31      295
## 3732            1.020704e-07                1.0000000         27      243
## 214             1.062720e-07                1.0000000         26      222
## 403             4.939242e-07                0.9999998         37      434
## 2166            7.025101e-07                0.9999998         30      315
## 4175            1.643157e-06                0.9999994         37      437
## 4538            1.829685e-06                0.9999994         29      317
## 1982            2.543725e-06                0.9999995         17      129
## 2404            2.968834e-06                0.9999993         19      161
## 1681            4.917748e-06                0.9999993         11       60
##               FDR
## 322  0.0001883494
## 3732 0.0001883494
## 214  0.0001883494
## 403  0.0006565488
## 2166 0.0007470492
## 4175 0.0013897761
## 4538 0.0013897761
## 1982 0.0016906235
## 2404 0.0017539214
## 1681 0.0026147665
## 
## [1] "ExM_nor_ISL1_CE_up"
## $reactome
##                        category over_represented_pvalue
## 746 olfactory signaling pathway             1.19631e-05
##     under_represented_pvalue numDEInCat numInCat        FDR
## 746                0.9999979         12       89 0.01586306
## 
## $go_bp
##                                      category over_represented_pvalue
## 713             defense response to bacterium            7.160612e-08
## 39                acute inflammatory response            7.647093e-07
## 427                              cell killing            6.358243e-06
## 1824               mononuclear cell migration            1.254278e-05
## 477      cellular response to biotic stimulus            2.129277e-05
## 2590 organ or tissue specific immune response            2.977281e-05
## 4679 response to molecule of bacterial origin            3.365707e-05
## 1502                      leukocyte migration            3.681582e-05
## 242         bile acid and bile salt transport            4.787034e-05
## 3882                regulation of endocytosis            5.033140e-05
##      under_represented_pvalue numDEInCat numInCat          FDR
## 713                 1.0000000         22      209 0.0003807297
## 39                  0.9999999         13       88 0.0020329797
## 427                 0.9999986         16      156 0.0112689261
## 1824                0.9999971         16      165 0.0166724907
## 477                 0.9999942         18      211 0.0226427321
## 2590                0.9999980          6       23 0.0244687119
## 4679                0.9999891         22      303 0.0244687119
## 1502                0.9999876         23      327 0.0244687119
## 242                 0.9999964          6       25 0.0267612058
## 3882                0.9999842         20      267 0.0267612058
## 
## [1] "ExM_nor_ISL1_CE_down"
## $reactome
##                                        category over_represented_pvalue
## 346           extracellular matrix organization            1.384967e-07
## 253     degradation of the extracellular matrix            6.390523e-05
## 950 response to elevated platelet cytosolic ca2            1.022845e-04
##     under_represented_pvalue numDEInCat numInCat          FDR
## 346                1.0000000         21      285 0.0001836466
## 253                0.9999877         11      134 0.0423691677
## 950                0.9999812         10      123 0.0452097438
## 
## $go_bp
##                                   category over_represented_pvalue
## 4552              renal system development            2.385023e-09
## 876  embryonic skeletal system development            8.918537e-09
## 165                appendage morphogenesis            2.262997e-08
## 5000    striated muscle tissue development            2.689309e-08
## 367             cardiocyte differentiation            3.751209e-08
## 164                  appendage development            9.020386e-08
## 335               cardiac cell development            1.004327e-07
## 2166     negative regulation of locomotion            1.305182e-07
## 869            embryonic organ development            1.567302e-07
## 4850            sensory system development            1.791237e-07
##      under_represented_pvalue numDEInCat numInCat          FDR
## 4552                        1         26      314 1.268117e-05
## 876                         1         15      115 2.370993e-05
## 165                         1         16      141 3.574764e-05
## 5000                        1         21      241 3.574764e-05
## 367                         1         16      143 3.989035e-05
## 164                         1         17      176 7.628578e-05
## 335                         1         12       81 7.628578e-05
## 2166                        1         23      315 8.674568e-05
## 869                         1         27      424 9.259271e-05
## 4850                        1         25      366 9.524008e-05
## 
## [1] "ExM_nor_ISL1_KO_up"
## $reactome
##                        category over_represented_pvalue
## 746 olfactory signaling pathway            1.080823e-08
##     under_represented_pvalue numDEInCat numInCat          FDR
## 746                        1         14       89 1.433171e-05
## 
## $go_bp
##                         category over_represented_pvalue
## 4847 sensory perception of smell            2.780553e-07
##      under_represented_pvalue numDEInCat numInCat        FDR
## 4847                        1         13      102 0.00147842
## 
## [1] "ExM_nor_ISL1_KO_down"
## $reactome
##                                    category over_represented_pvalue
## 346       extracellular matrix organization            3.418095e-07
## 253 degradation of the extracellular matrix            8.502496e-06
## 307                       ecm proteoglycans            8.988685e-05
## 956  reversible hydration of carbon dioxide            1.282475e-04
## 185                    collagen degradation            1.312697e-04
##     under_represented_pvalue numDEInCat numInCat          FDR
## 346                0.9999999         20      285 0.0004532394
## 253                0.9999986         12      134 0.0056371552
## 307                0.9999876          8       75 0.0348127142
## 956                0.9999980          3        7 0.0348127142
## 185                0.9999840          7       60 0.0348127142
## 
## $go_bp
##                                           category over_represented_pvalue
## 165                        appendage morphogenesis            1.587103e-09
## 876          embryonic skeletal system development            4.621993e-09
## 869                    embryonic organ development            1.528846e-08
## 371                          cartilage development            2.148341e-08
## 659                  connective tissue development            4.292037e-08
## 164                          appendage development            4.543318e-08
## 335                       cardiac cell development            5.801474e-08
## 4850                    sensory system development            6.577880e-08
## 4552                      renal system development            8.631775e-08
## 1022 external encapsulating structure organization            8.873752e-08
##      under_represented_pvalue numDEInCat numInCat          FDR
## 165                         1         17      141 8.438627e-06
## 876                         1         15      115 1.228757e-05
## 869                         1         28      424 2.709625e-05
## 371                         1         18      188 2.855682e-05
## 659                         1         21      263 4.026137e-05
## 164                         1         17      176 4.026137e-05
## 335                         1         12       81 4.371823e-05
## 4850                        1         25      366 4.371823e-05
## 4552                        1         23      314 4.718174e-05
## 1022                        1         22      302 4.718174e-05
## 
## [1] "ExM_nor_ISL1_PTC_up"
## $reactome
##                        category over_represented_pvalue
## 746 olfactory signaling pathway            3.342164e-08
##     under_represented_pvalue numDEInCat numInCat          FDR
## 746                        1         12       89 4.431709e-05
## 
## $go_bp
##                                                             category
## 4847                                     sensory perception of smell
## 5199                        tyrosine phosphorylation of stat protein
## 3634                             receptor signaling pathway via stat
## 3350 positive regulation of tyrosine phosphorylation of stat protein
##      over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 4847            8.376484e-07                0.9999999         11      102
## 5199            1.767983e-05                0.9999981          8       69
## 3634            2.896012e-05                0.9999949         11      145
## 3350            3.278102e-05                0.9999968          7       55
##              FDR
## 4847 0.004453776
## 5199 0.043574177
## 3634 0.043574177
## 3350 0.043574177
## 
## [1] "ExM_nor_ISL1_PTC_down"
## $reactome
##                                                                                                                    category
## 346                                                                                       extracellular matrix organization
## 307                                                                                                       ecm proteoglycans
## 253                                                                                 degradation of the extracellular matrix
## 950                                                                             response to elevated platelet cytosolic ca2
## 910 regulation of insulin like growth factor igf transport and uptake by insulin like growth factor binding proteins igfbps
##     over_represented_pvalue under_represented_pvalue numDEInCat numInCat
## 346            2.630596e-08                1.0000000         19      285
## 307            1.386547e-05                0.9999985          8       75
## 253            2.575236e-05                0.9999960         10      134
## 950            6.134437e-05                0.9999906          9      123
## 910            1.513934e-04                0.9999772          8      112
##              FDR
## 346 3.488171e-05
## 307 9.192807e-03
## 253 1.138254e-02
## 950 2.033566e-02
## 910 4.014954e-02
## 
## $go_bp
##                                   category over_represented_pvalue
## 165                appendage morphogenesis            2.243689e-10
## 164                  appendage development            5.927931e-09
## 876  embryonic skeletal system development            1.096842e-08
## 4850            sensory system development            2.860701e-08
## 371                  cartilage development            9.997279e-08
## 852      embryonic appendage morphogenesis            1.346438e-07
## 4552              renal system development            2.635309e-07
## 869            embryonic organ development            2.736724e-07
## 335               cardiac cell development            3.262088e-07
## 659          connective tissue development            3.366968e-07
##      under_represented_pvalue numDEInCat numInCat          FDR
## 165                 1.0000000         16      141 1.192969e-06
## 164                 1.0000000         16      176 1.575940e-05
## 876                 1.0000000         13      115 1.943970e-05
## 4850                1.0000000         22      366 3.802587e-05
## 371                 1.0000000         15      188 1.063111e-04
## 852                 1.0000000         12      117 1.193169e-04
## 4552                0.9999999         19      314 1.790217e-04
## 869                 0.9999999         22      424 1.790217e-04
## 335                 1.0000000         10       81 1.790217e-04
## 659                 0.9999999         17      263 1.790217e-04
file_tag = "2023_12"

saveRDS(goseq_res, sprintf("results/gene_set_enrichments_%s.rds", 
                           file_tag))
gc()
##            used  (Mb) gc trigger  (Mb) limit (Mb) max used  (Mb)
## Ncells  8857532 473.1   15591512 832.7         NA 15591512 832.7
## Vcells 22997502 175.5   73154941 558.2      65536 91443676 697.7
sessionInfo()
## R version 4.2.3 (2023-03-15)
## Platform: aarch64-apple-darwin20 (64-bit)
## Running under: macOS Ventura 13.4.1
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/4.2-arm64/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/4.2-arm64/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## attached base packages:
## [1] stats4    stats     graphics  grDevices utils     datasets  methods  
## [8] base     
## 
## other attached packages:
##  [1] TxDb.Hsapiens.UCSC.hg38.knownGene_3.16.0
##  [2] GenomicFeatures_1.50.4                  
##  [3] GenomicRanges_1.50.2                    
##  [4] GenomeInfoDb_1.34.9                     
##  [5] org.Hs.eg.db_3.16.0                     
##  [6] AnnotationDbi_1.60.2                    
##  [7] IRanges_2.32.0                          
##  [8] S4Vectors_0.36.2                        
##  [9] Biobase_2.58.0                          
## [10] BiocGenerics_0.44.0                     
## [11] data.table_1.14.8                       
## [12] dplyr_1.1.2                             
## [13] fgsea_1.24.0                            
## [14] goseq_1.50.0                            
## [15] geneLenDataBase_1.34.0                  
## [16] BiasedUrn_2.0.10                        
## [17] RColorBrewer_1.1-3                      
## [18] stringr_1.5.0                           
## [19] ggpubr_0.6.0                            
## [20] ggrepel_0.9.3                           
## [21] ggplot2_3.4.2                           
## 
## loaded via a namespace (and not attached):
##  [1] colorspace_2.1-0            ggsignif_0.6.4             
##  [3] rjson_0.2.21                XVector_0.38.0             
##  [5] rstudioapi_0.14             bit64_4.0.5                
##  [7] fansi_1.0.4                 xml2_1.3.4                 
##  [9] codetools_0.2-19            splines_4.2.3              
## [11] R.methodsS3_1.8.2           cachem_1.0.7               
## [13] knitr_1.44                  jsonlite_1.8.4             
## [15] Rsamtools_2.14.0            broom_1.0.4                
## [17] GO.db_3.16.0                dbplyr_2.3.2               
## [19] png_0.1-8                   R.oo_1.25.0                
## [21] compiler_4.2.3              httr_1.4.6                 
## [23] backports_1.4.1             Matrix_1.6-4               
## [25] fastmap_1.1.1               cli_3.6.1                  
## [27] htmltools_0.5.5             prettyunits_1.1.1          
## [29] tools_4.2.3                 gtable_0.3.3               
## [31] glue_1.6.2                  GenomeInfoDbData_1.2.9     
## [33] rappdirs_0.3.3              fastmatch_1.1-3            
## [35] Rcpp_1.0.10                 carData_3.0-5              
## [37] jquerylib_0.1.4             vctrs_0.6.2                
## [39] Biostrings_2.66.0           nlme_3.1-162               
## [41] rtracklayer_1.58.0          xfun_0.39                  
## [43] lifecycle_1.0.3             restfulr_0.0.15            
## [45] rstatix_0.7.2               XML_3.99-0.14              
## [47] zlibbioc_1.44.0             scales_1.2.1               
## [49] hms_1.1.3                   MatrixGenerics_1.10.0      
## [51] parallel_4.2.3              SummarizedExperiment_1.28.0
## [53] yaml_2.3.7                  curl_5.0.1                 
## [55] memoise_2.0.1               sass_0.4.5                 
## [57] biomaRt_2.54.1              stringi_1.7.12             
## [59] RSQLite_2.3.1               BiocIO_1.8.0               
## [61] filelock_1.0.2              BiocParallel_1.32.6        
## [63] rlang_1.1.0                 pkgconfig_2.0.3            
## [65] matrixStats_1.0.0           bitops_1.0-7               
## [67] evaluate_0.20               lattice_0.20-45            
## [69] purrr_1.0.1                 GenomicAlignments_1.34.1   
## [71] cowplot_1.1.1               bit_4.0.5                  
## [73] tidyselect_1.2.0            magrittr_2.0.3             
## [75] R6_2.5.1                    generics_0.1.3             
## [77] DelayedArray_0.24.0         DBI_1.1.3                  
## [79] pillar_1.9.0                withr_2.5.0                
## [81] mgcv_1.8-42                 KEGGREST_1.38.0            
## [83] abind_1.4-5                 RCurl_1.98-1.12            
## [85] tibble_3.2.1                crayon_1.5.2               
## [87] car_3.1-2                   utf8_1.2.3                 
## [89] BiocFileCache_2.6.1         rmarkdown_2.21             
## [91] progress_1.2.2              grid_4.2.3                 
## [93] blob_1.2.4                  digest_0.6.31              
## [95] tidyr_1.3.0                 R.utils_2.12.2             
## [97] munsell_0.5.0               bslib_0.4.2